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Fluid and Electrolyte Disturbances
Sodium retention
Congestive heart failure in susceptible patients
Hypertension
Fluid retention
Potassium loss
Hypokalemic alkalosis
Musculoskeletal
Muscle weakness
Loss of muscle mass
Steroid myopathy
Osteoporosis
Tendon rupture, particularly of the Achilles tendon
Vertebral compression fractures
Aseptic necrosis of femoral and humeral heads
Pathologic fracture of long bones
Gastrointestinal
Peptic ulcer with possible perforation and hemorrhage
Pancreatitis
Abdominal distention
Ulcerative esophagitis
Increases in alanine transaminase (ALT, SGPT), aspartate transaminase (AST, SGOT), and alkaline phosphatase have been observed following corticosteroid treatment. These changes are usually small, not associated with any clinical syndrome and are reversible upon discontinuation.
Dermatologic
Impaired wound healingPetechiae and ecchymoses
May suppress reactions to skin tests
Thin fragile skin
Facial erythema
Increased sweating
Neurological
Increased intracranial pressure with papilledema (pseudo-tumor cerebri) usually after treatment
Convulsions
Vertigo
Headache
Endocrine
Development of Cushingoid state
Suppression of growth in children
Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery or illness
Menstrual irregularities
Decreased carbohydrate tolerance
Manifestations of latent diabetes mellitus
Increased requirements of insulin or oral hypoglycemic agents in diabetics
Ophthalmic
Posterior subcapsular cataracts
Increased intraocular pressure
Glaucoma
Exophthalmos
Metabolic
Negative nitrogen balance due to protein catabolism
The following additional reactions have been reported following oral as well as parenteral therapy: Urticaria and other allergic, anaphylactic or hypersensitivity reactions.
Based on conventional studies of safety pharmacology and repeated-dose toxicity, no unexpected hazards were identified. The toxicities seen in the repeated-dose studies were those expected to occur with continued exposure to exogenous adrenocortical steroids.
There was no evidence of a potential for genetic and chromosome mutations in limited studies performed in bacteria and mammalian cells. Long-term studies in animals have not been performed to evaluate carcinogenic potential, as the drug is indicated for short-term treatment only.
Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. In animal reproduction studies, glucocorticoids such as Метипред have been shown to induce malformations (cleft palate, skeletal malformations) and intra-uterine growth retardation.
Pharmacotherapeutic group: Glucocorticoids, ATC code: H02AB04
Метипред is a corticosteroid with an anti-inflammatory activity at least five times that of hydrocortisone. An enhanced separation of glucocorticoid and mineralocorticoid effect results in a reduced incidence of sodium and water retention.
Метипред pharmacokinetics is linear, independent of route of administration.
Distribution
Метипред is widely distributed into the tissues, crosses the blood-brain barrier, and is secreted in breast milk.
The plasma protein binding of Метипред in humans is approximately 77%.
Metabolism
Метипред is extensively bound to plasma proteins, mainly to globulin and less to albumin. Only unbound corticosteroid has pharmacological effects or is metabolised. Metabolism occurs in the liver and to a lesser extent in the kidney. In humans, Метипред is metabolised in the liver to inactive metabolites; the major ones are 20α-hydroxyМетипред and 20β- hydroxyМетипред.
Metabolism in the liver occurs primarily via CYP3A2.
Elimination
Metabolites are excreted in the urine.
The mean elimination half-life for total Метипред is in the range of 1.8 to 5.2 hours. Its apparent volume of distribution is approximately 1.4 mL/kg and its total clearance is approximately 5 to 6 mL/min/kg. Mean elimination half-life ranges from 2.4 to 3.5 hours in normal healthy adults and appears to be independent of the route of administration.
Total body clearance following intravenous or intramuscular injection of Метипред to healthy adult volunteers is approximately 15-16l/hour. Peak Метипред plasma levels of 33.67 mcg/100 ml were achieved in 2 hours after a single 40 mg i.m. injection to 22 adult male volunteers. Метипред, like many CYP3A4 substrates, may also be a substrate for ATP-binding cassette (ABC) transport protein p-glycoprotein, influencing tissue distribution and interactions with other medicines.
No dosing adjustments are necessary in renal failure. Метипред is haemodialysable.
The effect of corticosteroids on the ability to drive or use machinery has not been systematically evaluated. Undesirable effects, such as dizziness, vertigo, visual disturbances, and fatigue are possible after treatment with corticosteroids. If affected, patients should not drive or operate machinery.
After reconstitution, the solution should be clear and colourless. Parenteral drug products should wherever possible be visually inspected for particulate matter and discoloration prior to administration.
The initially prepared solution may be diluted with 5% dextrose in water, isotonic saline solution, or 5% dextrose in isotonic saline solution. To avoid compatibility problems with other drugs, the reconstituted Метипред solution should be administered separately, only in the solutions mentioned.
